Current methods of chemotherapy and chemoprophylaxis of pyogenic bacterial infections leave much to be desired. Alternatives that are potentially applicable to man may be found among the antagonistic interactions of microorganisms that serve to maintain an ecologic stability within the microcosm. Investigations in this area must be designed (1) to detect naturally occurring antagonistic interactions between members of man's indigenous microflora and potential pyogenic pathogens, (2) to determine which may be applicable to a biologic situation by developing models for their study, and (3) to define the mechanisms of those interactions that may be applied to clinical situations. Specific goals, both immediate and long-term, of the research in progress are: (1) identification of microorganisms capable of inhibiting growth of either Group Astreptococci, meningococci, or pathogenic staphylococci, (2) selection of those strains that are capable of colonizing the skin or upper respiratory tract without causing disease, (3) demonstration of the extent to which the presence of these selected strains may contribute to host resistance to infection with pyogenic microorganisms in prospective studies and (4) determination of mechanisms of the observed antagonism. Having devised and evaluated techniques to identify antagonistic interactions, these will be applied to additional prospective clinical and epidemiologic studies to further elucidate the possible role of the normal throat flora in defense against infections, especially those due to the Group A streptococcus. The mechanism of inhibition of Group A streptococci by non-hemolytic streptococci, viridans streptococci and Neisseria will be evaluated by methods previously described.